It is of course well known to sterilize metal surgical instruments by steam and it has also been common practice to sterilize various articles in sterilizing liquids. High temperature steam sterilizing is simple and effective for certain metal objects, but has limitations and disadvantages, for example it is inefficient in sterilizing any object which a sealed package, and the high temperatures involved may cause degradation of plastic articles. The use of sterilizing liquids also has limitations, for example air bubbles may be trapped within the object thus preventing full effectiveness, and it may be difficult or impossible to remove all trace of the liquid afterwards.
It has also been common practice to sterilize medical or surgical equipment by means of a toxic gas and many existing sterilizers in hospital use, for example, involve contacting the articles with ethylene oxide in a sealed sterilizing chamber. Ethylene oxide is an extremely effective bactericide, and is effective not only for metal objects such as surgical implements, but also relatively delicate instruments and equipment, including synthetic plastics. The gas is effective at medium or low temperatures and thus the effects of high temperatures on degrading materials can be avoided. The gas penetrates or permeates plastic wrappings and can thus be used to sterilize pre-packaged objects.
Ethylene oxide is, however, extremely toxic to human beings and after its use for sterilizing it is important that steps be taken to remove all traces, as far as possible. To this end it is known to flush out the interior of the sterilizing chamber or autoclave with fresh air after the sterilizing gas has been extracted. It has also been proposed to "pulse" or vary the pressure of the flushing air during the flushing operation.
One of the problems involved is that the ethylene oxide is absorbed into a number of typical plastic materials which may need to be sterilized, and to "desorb" the gas from the plastics appears to be extremely difficult. Even after the sterilizing chamber has been flushed the desorption of the gas from the objects may result in contaminating the atmosphere of the laboratory or other workroom to a concentration of, say, 4 ppm or more which is an unacceptable health hazard.
Ethylene oxide sterilization is normally validated and monitored by biological measurements. This is achieved by demonstrating the killing of standardized preparations or biological indicators of known resistance to ethylene oxide. For routine process monitoring of production cycles after exposure to ethylene oxide, the biological indicators are placed in culture media and incubated to determine growth and survival. However, the incubation and inspection of the indicators typically takes several days and so does not allow real-time monitoring of the efficiency of the sterilization process. Also, whilst indicating whether the sterilizing process has been successful it does not indicate whether the concentration of ethylene oxide is much higher than necessary (i.e. an "overkill") or only just adequate. Nor can it indicate when it is safe to open the sterilizer.
The use of biological monitoring for quality control is less satisfying than parametric monitoring because of the inherent variability of biological monitors and associated recovery restraints.
In Yeung et al. ("On Line Measurement of the Gaseous Concentration and Relative Humidity in a 100% Ethylene Oxide Sterilisation Cycle", J. Parenteral Drug Association, Vol 33, No. 3, pp 117-124) there is proposed a sterilizer with a dual column gas chromatograph analyzer which samples the atmosphere within the chamber every 90 seconds or so and using a carrier or transfer gas, conveys the sample through the columns which are usually packed with an inert porous support material whereby the different gaseous components are separated and detected. However, whilst capable of regularly sampling the sterilizing chamber atmosphere, a gas chromatograph cannot provide proper real-time measurement of the constituents in the sample because the final measurement is dependent on the slow passage of the sample through the columns.
Also, a characteristic and limiting feature of a gas chromatography analyzer is that the columns cannot be sterilized, or more correctly, if the columns were sterilized it would render them useless for the purpose of measurement.
Furthermore, the act of sampling breaches the all-important sterility or barrier boundary after sterile conditions have been achieved, thus compromising the sterilization procedure.
Yeung et al. suggest that, to prevent the carrier gas from contaminating (either chemically or biologically) the sterilizing chamber, the samples are vented to waste rather than returned to the chamber. This inevitably creates a disposal problem and necessarily alters the in-chamber conditions being measured. Furthermore since there is no constant flow path from the sterilizer to the analyzer and back to the sterilizer, this further frustrates any attempt to obtain measurements in real-time.